June 17, 2013

Genetic Mutation Led To Famous Biker’s Rare Condition

An international team of scientists writing in the journal Nature Genetics has helped to identify a single genetic mutation in National Paracycling Champion Tom Staniford that has led to his extremely rare condition.

Staniford suffers a rare condition known as MDP Syndrome in which he is unable to store fat under his skin, despite having type 2 diabetes. Scientists had been baffled by Tom's condition, but advances in genome sequencing has at least helped them identify a gene mutation.

"In some ways, identifying the syndrome behind my symptoms shouldn't be important — a name is just a name, after all — but it is reassuring to know that there are other people with the condition and that we can lead relatively normal lives," says Tom Staniford. "What could prove crucial, though, is enabling me to be properly classified in competitions so that I am not competing at an unfair disadvantage against others. I hope to be able to compete for Great Britain in the 2016 Paralympics and this finding could make a real difference to my chances."

Tom was born a normal weight, but throughout his childhood and teenage years he lost all the fat around his face and limbs. Later on his hearing deteriorated throughout his childhood and now he has to wear hearing aids. His condition, which affects as few as eight people in the world, causes him to have no natural cushioning on his body, sore feet, and have a higher risk of breaking bones if he falls from his bike.

Professor Andrew Hattersley, a Wellcome Trust Senior Investigator at the University of Exeter Medical School, led a team of researchers in a study of four unrelated patients in the UK, US and India, all with the same symptoms. None of these patients had any family with a history of the condition, suggesting that their condition may have been caused by genetic mutations.

The team sequenced and compared the entire genomes of the participants and their families, helping them pinpoint the exact mutation responsible for MDP Syndrome. They found a single amino acid was missing from an enzyme, which is crucial to DNA replications.

"Tom's condition has been a puzzle to us for many years. We could see the symptoms, including the very unusual case of type 2 diabetes in someone with no obvious body fat, but did not know what was causing them," Hattersley said. "We had to look at thirty million base pairs in Tom's DNA, and similar numbers in his family members and the other patients, to identify the single mutation. This would not have been feasible even a couple of years ago, but new sequencing technology makes it possible for even patients with a rare genetic disorder to receive a diagnosis."

He said identifying this mutation has implications both for predicting the long term impact of the condition on Tom's health and on his sporting career. The researchers hope the genetic discovery will help scientists identify therapies that could make a significant difference for people with this rare and complex syndrome.

"This is a great example of genome sequencing coming of age," said Dr Michael Dunn, Head of Genetic and Molecular Sciences at the Wellcome Trust. "Where previously sequencing a patient's entire genome was prohibitively expensive, it is now far more cost effective. As we've seen here, it is no longer just about identifying genes implicated in common diseases, but is about informing diagnoses and prognoses of rare diseases — and, in Tom's case, helping inform his sporting performance."